These compounds inhibited PTP1B in the micromolar range, and characterization of the most potent inhibitor (compound 115, N-benzyl-N-(2-hydroxy-2-phenylethyl)-2, 4, 6-trimethyl benzene sulfonamide, Figure 7) showed that it improved oral glucose tolerance and enhanced insulin resistance by restoring the insulin level and normalizing the serum lipid profile when assessed in both C57BL/KsJ-db/db mice and an STZ-induced diabetic rat model. This evidence concerns the gene INS and diabetes mellitus.